RT Journal Article
SR Electronic
T1 Measuring Nonapoptotic Caspase Activity with a Transgenic Reporter in Mice
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0147-21.2022
DO 10.1523/ENEURO.0147-21.2022
VO 9
IS 5
A1 Nicholls, P. J.
A1 Pack, Thomas F.
A1 Urs, Nikhil M.
A1 Kumar, Sunil
A1 Zhou, Yang
A1 Ichim, Gabriel
A1 Ginzel, Joshua D.
A1 Turu, Gabor
A1 Calabrese, Evan
A1 Roberts, Wendy L.
A1 Fan, Ping
A1 Ostapchenko, Valeriy G.
A1 Guzman Lenis, Monica S.
A1 Beraldo, Flavio
A1 Hatina, Jiri
A1 Prado, Vania F.
A1 Prado, Marco A. M.
A1 Spasojevic, Ivan
A1 Snyder, Joshua C.
A1 Dzirasa, Kafui
A1 Johnson, G. Allan
A1 Caron, Marc G.
YR 2022
UL http://www.eneuro.org/content/9/5/ENEURO.0147-21.2022.abstract
AB The protease caspase-3 is a key mediator of apoptotic programmed cell death. But weak or transient caspase activity can contribute to neuronal differentiation, axonal pathfinding, and synaptic long-term depression. Despite the importance of sublethal, or nonapoptotic, caspase activity in neurodevelopment and neural plasticity, there has been no simple method for mapping and quantifying nonapoptotic caspase activity (NACA) in rodent brains. We therefore generated a transgenic mouse expressing a highly sensitive and specific fluorescent reporter of caspase activity, with peak signal localized to the nucleus. As a proof of concept, we first obtained evidence that NACA influences neurophysiology in an amygdalar circuit. Then focusing on the amygdala, we were able to quantify a sex-specific persistent elevation in caspase activity in females after restraint stress. This simple in vivo caspase activity reporter will facilitate systems-level studies of apoptotic and nonapoptotic phenomena in behavioral and pathologic models.